此外，目前的指南不建议将无症状的乙型肝炎病毒携带者进行抗HBV治疗，但这个群体需要有药物来实现慢性乙肝病毒感染的功能性治愈，因为HBV病毒血症会引起肝细胞癌和肝炎风险。 

 

日本爱媛大学等研究机构的科研人员发表在2019AASLD年会上的这项研究旨在评估含有HBsAg 和 HBcAg 的鼻用治疗性乙肝疫苗 NASVAC 对使用核苷（酸）类似物治疗的慢乙肝患者和无症状的乙型肝炎病毒携带者携带者的 HBsAg 动力学的功效。

 

在获得机构审查委员会的书面同意和许可并将研究纳入日本的临床试验机构之后，患有慢性乙型肝炎的患者和无症状乙肝病毒携带者在日本爱媛大学医院进行了开放标签的临床试验（IRB＃E18-27； 已注册到jRCT（＃jRCTs061180100）。将 NASVAC 在羧基乙烯基聚合物中乳化以增加粘度，之后通过专门设计用于鼻腔粘膜中使 NASVAC 持久存在的特殊装置给受试者每2周给药一次，共10次。研究人员分析了治疗结束后（EOT）6个月受试者的数据。

 

受试者基本情况：核苷（酸）类似物治疗的29例慢乙肝患者（NA组：年龄49-66岁，ALT：16-28 U / L，HBsAg：93-1942 IU / mL）和41例无活动性肝炎的HBV携带者（无症状组：年龄： （44-65岁，ALT：16-29 U / L，HBsAg：267-3267 IU / mL）。

 

在NA组中，有78.9％的患者表现出 HBsAg 降低，EOT后6个月的平均 HBsAg 降低为19. 9％。38.5％的患者血清中出现抗HBs。

 

NA组中有2例患者获得了功能性治愈。在无症状组中，有85.2％的患者出现 HBsAg 降低。 68.2％的无症状患者观察到 HBV-DNA 降低，并且3例患者表现出持续的HBV-DNA阴转。无症状组中有2例获得了功能性治愈。

 

综上，研究认为，NASVAC 可以诱导使用核苷（酸）类似物治疗的慢乙肝患者和无症状的乙型肝炎病毒携带者出现抗HBs，并使 HBsAg 降低。

 

总共有4例患者通过 NASVAC 治疗获得功能性治愈。 NASVAC 可能是实现慢性乙肝病毒感染者（包括慢乙肝患者和乙肝病毒携带者）功能性治愈的一种新的免疫疗法。

信息来源：2019AASLD论文集88 INDUCTION OF ANTI-HBS AND REDUCTION OF HBSAG BY NASAL ADMINISTRATION OF A THERAPEUTIC VACCINE CONTAINING HBSAG AND HBCAG (NASVAC) IN PATIENTS WITH CHRONIC HBV INFECTION

 

Osamu Yoshida1, Sheikh Mohamed Fazle Akbar2, Michinori Kohara3, Kyoko Tsukiyama-Kohara4, Takashi Miyazaki5,Taizou Kamishita5, Mamun Mahtab6, Julio C Aguilar7, Gerardo E Guillen7 and Yoichi Hiasa1, (1)Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, (2)Department of Pathology, Proteo-Science Center, Ehime University Graduate School of Medicine, (3)Department of Microbiology and Cell Biology,Tokyo Metropolitan Institute of Medical Science, (4)Joint Faculty of Veterinary Medicine, Kagoshima University, (5)Toko Yakuhin Kogyo Co., Ltd., (6)Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, (7)Vaccine Division, Biomedical Research Department, Center for Genetic Engineering and Biotechnology

 

Background: HBs antigen (HBsAg) loss with anti-HBs acquisition is regarded as functional cure and recognized as an ideal treatment goal for the patients with chronic hepatitis B virus (HBV) infection. However, it is difficult to achieve the functional cure in these patients by nucleos(t)ide analogs (NAs) or interferon. Further, HBV asymptomatic carrier, not recommended for anti-HBV therapy by current guidelines,needs drugs for achieving functional cure, because HBV viremia gives a risk for hepatocellular carcinoma and hepatic flare. This study was intended to assess the efficacy of nasal administrative therapeutic vaccine, NASVAC, containing both HBsAg and HBcAg, on kinetics of HBsAg in CHB patient under NAs and HBV asymptomatic carrier. 

 

Methods: CHB patient with and HBV asymptomatic carrier enrolled in an open-label clinical trial at Ehime University Hospital, Japan, after receiving

written consent and permission from institutional review board and enrollment of study to the clinical trial authority of Japan (IRB#E18-27; registered to jRCT (#jRCTs061180100) NASVAC was emulsified in carboxyl vinyl polymer to increase the viscosity, then administrated for 10 times, once in every 2 weeks, by a special device designed for durable existence of NASVAC in nasal mucosa. We analyzed the data at 6 months after end of treatment (EOT) 

 

Results: Twenty nine HBV patients under NAs treatment (NA group: age: 49-66years, ALT: 16-28 U/L, HBsAg: 93-1942 IU/mL) and forty one HBV carriers without active hepatitis (asymptomatic group: age: 44-65 years, ALT: 16-29 U/L, HBsAg: 267-3267 IU/mL) were enrolled In NA group, 78 9% of patients displayed HBsAg reduction, and the mean HBsAg reduction was 19 9% at 6 months after EOT 38 5% of patients showed anti-HBs in sera Two patients in NA group received functional cure In asymptomatic group, 85 2% of patients showed HBsAg reduction. HBV-DNA reduction was observed in 68.2% asymptomatic patients and 3 patients showed sustained HBV-DNA negativity. Two patients in asymptomatic group achieved functional cure 。

 

Conclusion: NASVAC induced anti-HBs, and reduced HBsAg in both CHB patients with NAs and asymptomatic HBV carrier. Overall 4 patients achieved

functional cure by NASVAC. NASVAC could be a novel immune therapy for achieving functional cure in HBV infected patients。